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30. Yang J, Dolinger M, Ritaccio G, Mazurkiewicz J, Conti D, Zhu X, Huang Y: Leucine stimulates insulin secretion via down-regulation of surface expression of adrenergic α2A receptor through the mTOR (mammalian target of rapamycin) pathway: implication in new-onset diabetes in renal transplantation. J Biol Chem 2012,287(29):24795–24806.PubMedCentralPubMedCrossRef 31. Hyun E, Ramachandran R, Hollenberg MD, Vergnolle N: Mechanisms behind the anti-inflammatory actions of insulin. Crit Rev Immunol 2011,31(4):307–340.PubMedCrossRef Competing learn more interests The authors declare that they have no competing interests. Authors’ contributions XW and CN carried out the animal studies and participated in the samples measurement. XW drafted the manuscript. JL performed the statistical analysis and helped to draft the manuscript. NL and JL sconceived of the study, and participated in its selleck products design and coordination. All authors read and approved the final manuscript.”
“Introduction Hepatoblastoma

is a rare malignant tumor of the liver that occurs in young infants with a median age at diagnosis of 16 months [1]. Hepatoblastoma accounts for 1% of new cancer diagnoses in childhood and is the most common childhood liver cancer [2]. While most cases of hepatoblastoma (HB) are sporadic and its aetiology is unknown, there is a close association of HB with developmental syndromes such as the Beckwith-Wiedemann Syndrome (BWS) and Familial Adenomatous Polyposis (FAP) [3, 4]. Several distinct histological subtypes of hepatoblastoma exist.

These include wholly epithelial tumours, with pure fetal and mixed fetal/embryonal histology; tumours with mixed epithelial and mesenchmyal features; and several types of Proteasome inhibitor transitional, small and large cell undifferentiated tumours [5]. This heterogeneous tumour spectrum appears to reflect distinct patterns of hepatic embryogenesis, indicating a developmental origin for HB, and such tumour heterogeneity may account for their variation in clinical behaviour [6]. Of several distinct developmentally regulated pathways known to be active in hepatoblastoma, such as IGF2/H19 [7, 8], Notch [9], and Wnt/β-catenin [9, 10], it is the Wnt/β-catenin pathway that is most closely implicated in its origin [9–15]. A common immunohistochemical finding in HB is the aberrant accumulation of β-catenin protein in the cytoplasm or nucleus [11, 12, 16]. Several previous studies of sporadic HB have identified mutations or deletions clustered in exon 3 of CTNNB1, the gene for β-catenin [11–13, 15, 17–19]. In the absence of Wnt selleck inhibitor activation, β-catenin is phosphorylated at specific N-terminal serine and threonine residues by the APC/Axin/GSK3β protein complex resulting in its ubiquitination and subsequent degradation, thus maintaining tight control of β-catenin levels within normal cells [20]. Wnt ligand binding inhibits serine/threonine phosphorylation of β-catenin, leading to its cytoplasmic accumulation.